Propranolol treatment in life-threatening airway hemangiomas: a case series and review of literature

Abstract

Objectives: Infantile hemangiomas (IHs) in the airway may be potentially life-threatening during the proliferative phase. Available treatments like oral corticosteroids (OCS) and chemotherapeutic agents usually showed variable responses and serious side effects. Propranolol is a new and promising treatment option.

Methods: A case series of five IH patients with airway involvement is presented, supplemented with a review of literature. Propranolol treatment (2.0-3.0mg/kg/day) was initiated between 3 weeks and 6 months of age. Three cases were treated with propranolol monotherapy, 2 cases with OCS primarily and propranolol secondarily, in which treatment with OCS could be reduced rapidly.

Results: In our case series a dramatic, fast response was observed in all cases, with a permanent effect after discontinuation in four cases. In one patient a relapse of airway problems occurred two months after discontinuation of propranolol at 16 months of age; this resolved after re-start of propranolol. Review of literature together with these five cases showed 81 patients with airway IHs treated with propranolol. Propranolol was effective in 90% of the cases and seven patients were classified as non-responders. Eight IHs relapsed while weaning of propranolol or after discontinuation; dose adjustment or restart was effective in most cases but one patient appeared resistant to therapy.

Conclusions: Propranolol seems to be a rapidly effective and safe treatment strategy for most IHs obstructing the airway. Because of the fast and important effects of propranolol, randomized controlled trials are hardly justifiable for this specific, relatively rare but, acute treatment indication. Despite the efficacy of propranolol, close monitoring of the patients with an airway IH is required, considering the risk of relapse of symptoms during or after treatment and the reported resistance to propranolol in at least 9% of the published cases. The dose and duration of treatment should be high and long enough to prevent relapse. Further research should focus on the optimal treatment protocol; the actual percentage of non-responders and also the mechanism of resistance to propranolol is unknown and needs to be illuminated.

Keywords: Adrenergic beta-antagonist; Airway obstruction; CT; Corticosteroids; ECG; ENT; GLUT1; IHs; Infantile hemangioma; LV; MRI; OCS; PHACES; Propranolol; RAS; RCTs; SPECT; Treatment; VEGF; acronym for posterior fossa brain malformations, hemangiomas of the face, arterial cerebrovascular abnormalities, eye abnormalities and sternal defects; bFGF; basic fibroblast growth factor; computed tomography; ear nose and throat; electrocardiography; glucose transporter protein 1; infantile hemangiomas/hemangiomas of infancy; left ventricle; magnetic resonance imaging; oral corticosteroids; randomized controlled trials; renin–angiotensin system; single photon emission computed tomography; vascular endothelial growth factor.